Ceramide-Phospholipid Risk Score Associates With Cardiovascular Events and Is Lowered by Atorvastatin, Simvastatin, and Anti-PCSK9 Treatments

OBJECTIVE: The aim of the study was to investigate the prognostic value of previously established ceramide-phospholipid risk score, CERT2, and its response to lipid-lowering treatments in patients with symptomatic or suspected coronary heart disease. APPROACH AND RESULTS: Selected ceramides and phospholipids were analyzed with a quantitative liquid chromatography-mass spectrometry-based method from plasma or serum samples obtained from the Angiography and Genes study (ANGES, N = 966), and placebo-controlled trials investigating atorvastatin and simvastatin (N = 44) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor RG7652 (N = 78). In the ANGES, the adjusted hazard ratios (95% confidence interval) per SD for the CERT2 risk score were 1.71 (1.42-2.08) for cardiovascular disease death, 1.36 (1.13-1.64) for myocardial infarction, 1.40 (1.20-1.63) for heart failure, 1.23 (1.08-1.40) for atrial fibrillation, 1.09 (0.89-1.33) for stroke, and 1.52 (1.06-2.18) for venous thromboembolism. The median decrease of the CERT2 risk score was 2 points by statin treatment ( P ≤ 0.001) and 3 points by PCSK9 inhibition ( P < 0.001) on the 0-12 scale. CONCLUSIONS: The CERT2 risk score is a significant predictor of cardiovascular outcomes in all-comer patients with symptomatic or suspected coronary heart disease. Treatment with lipid-lowering medication significantly lowers the CERT2 risk score.